This proposal is designed to determine the mechanisms of increased bone resorption and hypercalcemia which occur in humans and animals with malignant disease by using a combination of in vitro techniques and clinical studies. The project also is aimed to characterize the chemotactic factors released by remodeling or resorbing bone which cause unilateral migration of human and animal cells and to examine the effects of the new diphosphonate agent dichloromethane diphosphonate which decreases serum calcium in patients with hypercalcemia and may relieve bone pain in patients with osteolytic bone disease.